Cellular and Molecular Basis for Acute Nongenomically Mediated Actions of SERMs

Dı́az, Mario; Marrero-Alonso, Jorge; Marrero, Benito García; Marín, Raquel; Gómez, Tomás; Alonso, Rafael

doi:10.1007/3-540-34742-9_4

Cited by 3 publications

(2 citation statements)

References 89 publications

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“…One example is the selective estrogen receptor modulators (SERMs). In addition to their estrogen receptor mediated anticancer genomic effects, SERMs share with antipsychotic drugs amphiphilic structure,65 calmodulin antagonist actions,65 and strongly upregulate expression of a similar set of cholesterol homeostasis genes to antipsychotic drugs,42 yet SERMs do not cause extrapyramidal or metabolic side effects 66. Hence, the findings of our study provide a rationale for future research investigating the effectiveness of combining statins with a broader range of amphiphilic compoundsas codrugs to augment standard anticancer chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Extreme thermophilic ethanol production from rapeseed straw: Using the newly isolated Thermoanaerobacter pentosaceus and combining it with Saccharomyces cerevisiae in a two‐step process

Tomás

Karagöz

Karakashev

et al. 2013

Biotech & Bioengineering

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The newly isolated extreme thermophile Thermoanaerobacter pentosaceus was used for ethanol production from alkaline-peroxide pretreated rapeseed straw (PRS). Both the liquid and solid fractions of PRS were used. T. pentosaceus was able to metabolize the typical process inhibitors present in lignocellulosic hydrolysate, namely 5-hydroxymethyl furfural (HMF) and furfural, up to concentrations of 1 and 0.5 g L(-1) , respectively. Above these levels, xylose consumption was inhibited up to 70% (at 3.4 g-furfural L(-1) ) and 75% (at 3.4 g-HMF L(-1) ). T. pentosaceus was able to grow and produce ethanol directly from the liquid fraction of PRS, without any dilution or need for additives. However, when the hydrolysate was used undiluted the ethanol yield was only 37% compared to yield of the control, in which pure sugars in synthetic medium were used. The decrease of ethanol yield was attributed to the high amounts of salts resulting from the alkaline-peroxide pretreatment. Finally, a two-stage ethanol production process from PRS using Saccharomyces cerevisiae (utilization of hexoses in the first step) and T. pentosaceus (utilization of pentoses in the second step) was developed. Results showed that the two strains together could achieve up to 85% of the theoretical ethanol yield based on the sugar composition of the rapeseed straw, which was 14% and 50% higher compared to the yield with the yeast or the bacteria alone, respectively.

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Section: Discussionmentioning

confidence: 99%

Extreme thermophilic ethanol production from rapeseed straw: Using the newly isolated Thermoanaerobacter pentosaceus and combining it with Saccharomyces cerevisiae in a two‐step process

Tomás

Karagöz

Karakashev

et al. 2013

Biotech & Bioengineering

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“…TX is a triphenylethylene molecule that competes the binding of 17β-estradiol to estrogen receptors (ER) and prevents the transcriptional activation of estrogen-dependent genes, which control the proliferation of mammary gland cells. However, tamoxifen is known to significantly enhance the risk of developing endometrial lesions, including hyperplasia, polyps, carcinomas, sarcoma, as well as womb cancer and thromboembolism [5][6][7][8][9][10]. Notably, tamoxifen-associated endometrial cancer often has a poor clinical outcome, and serious concerns exist on its use for cancer prevention or long-term palliative treatment [9,11].…”

Section: Introductionmentioning

confidence: 99%

FLTX2: A Novel Tamoxifen Derivative Endowed with Antiestrogenic, Fluorescent, and Photosensitizer Properties

Dı́az

Lobo

Hernández

et al. 2021

IJMS

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Tamoxifen is the most widely used selective modulator of estrogen receptors (SERM) and the first strategy as coadjuvant therapy for the treatment of estrogen-receptor (ER) positive breast cancer worldwide. In spite of such success, tamoxifen is not devoid of undesirable effects, the most life-threatening reported so far affecting uterine tissues. Indeed, tamoxifen treatment is discouraged in women under risk of uterine cancers. Recent molecular design efforts have endeavoured the development of tamoxifen derivatives with antiestrogen properties but lacking agonistic uterine tropism. One of this is FLTX2, formed by the covalent binding of tamoxifen as ER binding core, 7-nitrobenzofurazan (NBD) as the florescent dye, and Rose Bengal (RB) as source for reactive oxygen species. Our analyses demonstrate (1) FLTX2 is endowed with similar antiestrogen potency as tamoxifen and its predecessor FLTX1, (2) shows a strong absorption in the blue spectral range, associated to the NBD moiety, which efficiently transfers the excitation energy to RB through intramolecular FRET mechanism, (3) generates superoxide anions in a concentration- and irradiation time-dependent process, and (4) Induces concentration- and time-dependent MCF7 apoptotic cell death. These properties make FLTX2 a very promising candidate to lead a novel generation of SERMs with the endogenous capacity to promote breast tumour cell death in situ by photosensitization.

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Cytotoxic effects of antipsychotic drugs implicate cholesterol homeostasis as a novel chemotherapeutic target

Wiklund

Catts

et al. 2009

Intl Journal of Cancer

105

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The reported reduction in cancer risk in those suffering from schizophrenia may be because antipsychotic medications have antineoplastic effects. In this study, 6 antipsychotic agents with a range of structural and pharmacological properties (reserpine, chlorpromazine, haloperidol, pimozide, risperidone and olanzapine), were screened for their effect on the viability of cell lines derived from lymphoblastoma, neuroblastoma, non-small cell lung cancer and breast adenocarcinoma. We aimed to determine if antipsychotic drugs in general possess cancer-specific cytotoxic potential, and whether it can be attributed to a common mode of action. With the exception of risperidone, all drugs tested displayed selective inhibition of the viability of cancer cell lines compared with normal cells. Using Affymetrix expression microarrays and quantitative real-time polymerase chain reaction, we found that for the antipsychotic drugs, olanzapine and pimozide, cytotoxicity appeared to be mediated via effects on cholesterol homeostasis. The role of cholesterol metabolism in the selective cytotoxicity of these drugs was supported by demonstration of their increased lethality when coadministered with a cholesterol synthesis inhibitor, mevastatin. Also, pimozide and olanzapine showed accelerating cytotoxic effects from 12 to 48 hr in time course studies, mirroring the time-dependent onset of cytotoxicity induced by the amphiphile, U18666A. On the basis of these results, we concluded that the Class II cationic amphiphilic properties of antipsychotic drugs contribute to their cytotoxic effects by acting on cholesterol homeostasis and altering the biophysical properties of cellular membranes, and that drugs affecting membrane-related cholesterol pathways warrant further investigation as potential augmentors of standard cancer chemotherapy.

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Cellular and Molecular Basis for Acute Nongenomically Mediated Actions of SERMs

Cited by 3 publications

References 89 publications

Extreme thermophilic ethanol production from rapeseed straw: Using the newly isolated Thermoanaerobacter pentosaceus and combining it with Saccharomyces cerevisiae in a two‐step process

Extreme thermophilic ethanol production from rapeseed straw: Using the newly isolated Thermoanaerobacter pentosaceus and combining it with Saccharomyces cerevisiae in a two‐step process

FLTX2: A Novel Tamoxifen Derivative Endowed with Antiestrogenic, Fluorescent, and Photosensitizer Properties

Cytotoxic effects of antipsychotic drugs implicate cholesterol homeostasis as a novel chemotherapeutic target

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